Formation of Five-membered Nitrogen Heterocycles

Periodate oxidation of 2-acetamido-1,2-dideoxy-3,4-0-isopropylidene-D-glucitol (33) affords 4-acetamido-4,5-dideoxy-2,3-0-isopropylidene-aldehydo-c-xylose, which, on hydrolysis with acetic acid, gives31 the pyrrolidine 34. The same series of reactions was performed31 on the 

Nuclear magnetic resonance (n.m.r.) studies have revealed that 4-amino-4-deoxy-L-xylose,35,350 4-amino-4,5-dideoxy-L-xylose,356 and 4-amino-4-deoxy-D-glucose34 (40) exist as equilibrium mixtures for example, of the pyrrolidine 40, the pyrroline 39 formed by its dehydration, and a dimer (41), the equilibrium lying strongly towards the last. Similar studies have shown that the hydrochlorides of 4-amino- 

4-deoxy-D-glucose34 and 4-amino-4,6-dideoxy-D-glucose36 exist preponderantly in the pyranose form thus, the latter consists, in solution, mainly of 42, with very little of 43. 

The conversion of 3-amino-3-deoxy sugars into pyrrolidines requires the presence of a leaving group, such as a p-tolylsulfonyloxy group on C-6 this is exemplified by the conversion of 3-azido-3-deoxy-l,2-0-isopropylidene-6-0-p-tolylsulfonyl-a-D-glucofuranose (44) and methyl 3-azido-2-benzamido-2,3-dideoxy-6-0-p-tolylsulfo-nyl-j8-D-glucopyranoside (46) into the respective pyrrolidines, 45 and 47, by reduction of the azido group, followed by cyclization.37 

Cyclization between a 1-amino group and C-4 of an anhydropenti-tol has been achieved 2,5-anhydro-l-azido-l-deoxy-3,4-di-0-p-toIyl-sulfonyl-D-xylitol (48) was hydrogenated to the 1-amino compound and then this was N-p-toluenesulfonylated, giving 49 the product was cyclized by use of sodium methoxide to38,39 the bicyclic compound (50). 

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The intense interest in the formation of five-membered nitrogen heterocycles by a 1,3-dipolar cycloaddition of an azomethine ylide, or related species, and an alkene or alkyne has been maintained this year. The majority of synthetic effort continues to be directed towards the mild generation of non-stabilized azomethine... 

Interaction of 258 with anilines or five-membered nitrogen heterocycles produced 265 and 266 via an aminoalkylation . Bicyclic derivatives 267-271 with an aminal structure resulted from the interaction of 258 with amides, urethanes, imides, ureas, amines or hydrazines. Finally, 272 was formed with carbon acids and a reduction to 273 occurred with the sodium salt of formic acid " . It is not yet totally clear whether an iminium ion is involved in the formation of 259-273. The yields of isolated products varied from 45 to 95 %. 

Cyclic structures form on polymer backbones through 1,3-dipolar additions to caibon-to-caibon or carbon-to-nitrogen double bonds. Because many 1,3-dipoles are heteroatoms, such additions can lead to formations of five-membered heterocyclic rings. An example is addition of nitrilimine to an unsaturated polyesters ... 

The insertion of CO into Pd-carbon bonds has also been employed in several tandem/cascade reactions that afford five-membered nitrogen heterocycles [97]. A representative example of this approach to the construction of heterocydes involves synthesis of isoindolinones via the Pd-catalyzed coupling of 2-bromobenzaldehyde with two equivalents of a primary amine under an atmosphere of CO [97bj. As shown below (Eq. (1.57)), this method was used for the preparation of 144 in 64% yield. The mechanism of this reaction is likely via initial, reversible condensation of 2-bromobenzaldehyde with 2 equiv of the amine to form an aminal 145. Oxidative addition of the aryl bromide to Pd° followed by CO insertion provides the acylpalladium spedes 146, which is then captured by the pendant aminal to afford the observed product. An alternative mechanism involving intramolecular imine insertion into the Pd—C bond of a related acylpalladium species, followed by formation of a paUadium-amido complex and C—N bond-forming reductive elimination has also been proposed [97b],... 

Reports on the synthesis of five-membered heterocycles by intramolecular nitrogen—nitrogen bond formation (N1—N5) came some years ago from our laboratory [79CC891 81 JCS(Pl) 1891 83JCS(P1)2273]. Thus, 4-alkyl(aryl)amino-l-azabutadienes 2, which are readily available in large scale from alkyl(aryl)imines 1 and aliphatic or aromatic nitriles (70S 142 ... 

The formation of pyrrole and its benzo analogs from other heterocyclic systems can occur in any of several general ways. In this section we will consider reactions which change the ring size and composition. In Section 3.06.6, reactions where the five-membered nitrogen-containing ring remains intact will be considered. 

Formation of annulated five-membered nitrogen-containing heterocycles is also observed in reactions of hydrazino-substituted pyrazino[2,3-d]pyridazines.92 Pyridazine-4,5-diamines 7 are formed when pyrazino[2,3-tf]pyridazines 6 substituted in the 5- and 8-positions are treated with hydrazine hydrate under reflux and a fast stream of air is passed through the reaction mixture. The splitting of the pyrazine ring is supposed to be initiated by the diimide formed under these conditions."... 

In 2013, Carreira and coworkers presented an attractive strategy for the synthesis of chiral pyrrolidones via ruthenium-catalyzed intramolecular hydrocar-bamoylation of allylic formamides under CO atmosphere (Eq. (7.2)) [7]. A formal ruthenium-catalyzed intramolecular insertion into the formamide C-H bond and concomitant C-C bond formation by olefin hydrocarbamoylation were involved in the reaction, which made the reaction complete atom economy. The cycliza-tion performed with a broad substrate scope. More interestingly, even homoallylic and bis-homoallylic formamide substrates were used, the reactions afforded five-membered nitrogen-containing heterocycles only. 

Despite the availability of various existing synthetic procedures, apphcation of RCM in the synthesis of polyhydroxyindolizidines recently became increasingly popular. The skeletons of all alkaloids described below were produced according to the same strategy involving N-alkenylation and RCM for the formation of five- and six-membered nitrogen heterocycles (Scheme 2.17). 

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